Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• achieved within 40 minutes at 25 Hz in the presence of ethyl acetate although the integrity of the vessel was compromised and significant levels of metallic copper were removed from the walls during work-up. Expeditious displacement of tosylate or halides from 5′-derivatised nucleosides was achieved using

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• proceed via an SN2 reaction of a cyclic intermediate such as I1, judging from the syn selectivity of the dioxytosylation [52][53]. The attack of the tosylate ion on I1 possibly takes place at the benzylic position or at the methylene carbon atom. The positive charge of I1 may be stabilized by the aryl

• styrene with 4a–e preferentially gave (S)-3, which forms via an electrophilic addition of the iodane toward the Si face of styrene, followed by an SN2 reaction with the tosylate ion. If an SN1 mechanism were involved in the oxytosylation of I1, the enantiomeric ratio of 3 would decrease owing to the

• planar structure of the benzylic cation. Thus, the tosylate ion may act as an effective nucleophile for the SN2 reaction of I1. The stereoface-differentiation in the dioxytosylation reaction using the lactate-derived aryl-λ3-iodanes is similar to that in preceding reactions [14], which include the

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• advantages of solution chemistry and solid-phase methods. Thus, solid-supported acyl chloride or pyridinium tosylate as the activator of nucleoside-3'-O-H-phosphonates/phosphoramidites, and polystyrene-bound trimethylammonium periodate as oxidation reagent have been demonstrated to be superior for dimer and

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• cycloaddition reaction of 1-phenylpyrrole (1a) using phenyl(mesityl)iodonium tosylate (2a) as benzyne precursor. To our delight, with LiHMDS as the base in toluene, the Diels–Alder adduct 3aa was obtained in 23% yield at room temperature (Table 1, entry 1). However, when the reaction temperature was increased

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• extend the carbon chain by one atom. The alcohol 11 was first converted into the corresponding tosylate (Scheme 1), but when this tosylate was subsequently treated with cyanide the undesired disubstituted product 14 was formed in 40% yield. Unfortunately, despite varying the reaction stoichiometry it was

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• terminal group (Figure 1) [20]. The functionalization of mPEG was also corroborated by the observed shift in the 1H NMR signals of the tosylate group protons from 7.92 (2H) and 7.49 (2H) in TsCl to 7.79 and 7.34 ppm, in mPEG–OTs (Figure S1, Supporting Information File 1) [20]. Employing NaOH as a base

• mPEG with tosylate functionality. TsCl = p-toluenesulfonyl chloride; CEA = chloroethylamine·HCl; Mw = molecular weight. All reactions were ball-milled at an operating frequency of 30 Hz. Surveyed reactions of mechanochemical derivatization to afford mPEG–Br, –SH, –COOH and –NH2 derivatives. Supporting

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• mechanochemistry offers significant challenges. For instance, the molecular weight negatively affects the reaction design and is almost one order of magnitude higher here than for common organic molecules. The laborious preparation of the starting CD-tosylate [24][25], and the considerable reactant molecular mass

• ]. Despite the longer milling times, using less balls allow outcomes to be improved [14]. This work takes the above-mentioned results as a base from which to address the mechanochemical synthesis of 6I-monoazido-6I-monodeoxy-β-CD and 6I-S-monodeoxy-6I-monothiouronium-β-CD tosylate (TU-β-CD), an important CD

• intermediate for the preparation of 6I-S-monodeoxy-6I-monothio-β-CD [26]. Having selected the 6I-O-monotosyl-β-CD (Ts-β-CD) as the benchmark, the nucleophilic displacement of the tosylate group in the presence of azido or thiourea (TU) nucleophiles was chosen for the study under different milling conditions

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• resulting tosylate and subsequent epoxidation of the obtained tosyloxy alcohol with anhydrous K2CO3 in absolute ethanol (Scheme 10) provided compound 5. The NMR spectra and specific rotations of 5 also matched those reported in the literature [17][18][19][36]. Conclusion In summary, in the context of

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• ′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the

• ball-milling chemistry on nucleoside substrates has not, to the authors’ knowledge, been demonstrated, despite reports of similar chemistry on glycoside derivatives [16][23] and α-amino acid analogues [24]. We describe here the efficient displacement of 5'-chloride, iodide or tosylate leaving groups

• -dependency also observed with KSeCN under Finkelstein conditions [38]. Finally, our approach also offers the convenience of employing tosylate and halide precursors rather than relying on the esoteric tresylate leaving group system. Model reactions of 5′-chloro-5′-deoxyadenosine (1a) with 4

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• , tosylate, or aryliodide (as Ar2I+)) using Pd-based catalysts. These methods achieve coupling of aryl C–C bonds with high activity and selectivity; however, the reactants are quite expensive and there is significant opportunity to improve the atom efficiency. Additionally, there is impetus to utilize less

• direct arylation reaction can be achieved with X = halogen, triflate, tosylate [14], B(OH)2 [15][16][17][18][19][20], SnR3 [21], Si(OR)3 [22], or with the use of aryliodonium salts [23]; wherein halogen atoms represent the most cost-effective and atom-efficient functional group. The reactions typically

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• an sp3 carbon increased the yield of the transetherification reaction significantly. Attempts were also made to attach an alkyne to EDOT via the reaction between hydroxymethyl EDOT and propargyl tosylate using DABCO as catalyst, but it led to a very low yield and this EDOT-propargyl product was very

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• tosylate to yield compounds 5a,b in high yields of 87% and 81%, respectively. These derivatives can be utilized for both variants of the Staudinger ligation in addition to the classical and strain-promoted variants of the Huisgen-click reaction. For future radiolabeling procedures, nitro derivatives 4a and

• dried over Na2SO4 and the solvent was removed to yield 931 mg of compound 3b. Spectra are in agreement with those found in the literature [46]. 4-(But-3-yn-1-yl)-1-(4-nitrobenzoyl)piperazine (4a): Compound 3a (110 mg, 0.47 mmol), but-3-yn-1-yl tosylate (150 mg, 0.67 mmol) and Et3N (100 mg, 0.98 mmol

• -yn-1-yl)-1-(4-fluorobenzoyl)piperazine (4b): Compound 3b (70 mg, 0.34 mmol), but-3-yn-1-yl tosylate (90 mg, 0.40 mmol) and Et3N (51 mg, 0.50 mmol) were dissolved in anhydrous THF (6 mL) and the resulting mixture was stirred at 60 °C for 3 d. After reaction control by TLC, THF was changed by ethyl

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• . Results and Discussion The synthesis of mixed tetraesters from the tetraalkylammonium salt of medronic acid trimethylester and alkyl tosylate utilizes a similar strategy used previously for the synthesis of monoesters (Scheme 2). The starting point for the synthesis was tetramethyl methylene-BP, from

• which one of the methyl groups was removed by selective demethylation with tributylamine. The resulting mono N,N,N,tributyl-N-methylammonium salt of the triester was then refluxed with the desired alkyl tosylate in acetonitrile. The resulting mixed tetraesters 2a–g were purified by column chromatography

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• high stereoselectivity (ee >90%) to give THF diol 32. The latter could be almost quantitatively converted to the corresponding tosylate, an intermediate in Brown`s synthesis of cis-solamin A (29) [76][78], thus completing a formal synthesis of this natural product (Scheme 8). In 2006, our group

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• substitution of monohalogenated and monotosylated CDs (Scheme 8) . The 6I-azido-6I-deoxy-β-CD, an extremely versatile intermediate, has been obtained from the displacement of the tosylate group under MW. The reaction time was cut from several hours to 2 min (200 W max, 85 °C) and the formation of side products

• was reduced [15]. 6I-(p-Toluenesulfonyl)-β-CD was converted to 6I-formyl-β-CD via DMSO oxidation in MW with collidine in 15 min (110 W, 135 °C). MW irradiation promoted the syntheses of 6I-deoxy-6I-thio-β-CD and 6I,6IV-dideoxy-6I,6IV-dithio-β-CD via nucleophilic substitution of the primary tosylate

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• conditions [48] and an ensuing desilylation furnished a diol. In order to introduce a leaving group for the following key step, the secondary hydroxy group was tosylated to afford 79. Once again, a stereospecific Grob fragmentation of tosylate 79 served as the key step for the synthesis of the

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• benzylated using BnBr and NaH in DMF to afford 3a (Scheme 1). Further, the C6-tosyl intermediate was converted into 6-azido-6-deoxy-1,2;3,4-di-O-isopropylidene-β-D-psicofuranose (4a) by a nucleophilic displacement of the C6-O-tosylate with NaN3 in DMF at 70 °C [48]. The spectral data and the specific

Two strategies for the synthesis of the biologically important ATP analogue ApppI, at a multi-milligram scale

• Janne Weisell,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2015, 11, 2189–2193, doi:10.3762/bjoc.11.237

• organic addition and substitution reactions [8]. In method B, the bis(tetrabutylammonium) salt of ATP was treated with isopentenyl tosylate to produce ApppI. The crude products were purified by an ion-pair chromatographical approach, based on the method first reported by Ryu and Scott [7], using

• quadrupole time-of-flight mass spectrometer using electrospray ionization (ESI) in the positive ionization mode. The purity of the products was determined from 1H and 31P NMR spectra and was ≥95% unless stated otherwise. Procedure for the preparation of isopentenyl tosylate (7): 3-Methyl-3-buten-1-ol (770 µL

• hygroscopic solid after evaporation of appropriate fractions in vacuo. Method B: ATP bis(tetrabutylammonium) salt (187 mg, 0.189 mmol) was dissolved in dry acetonitrile (1 mL) and isopentenyl tosylate 7 (48 mg, 0.200 mmol) was added and the reaction mixture stirred for 24 h at 40 °C before the reaction

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• 1 the dimer 2 is obtained in 88% material yield and 90% current yield. Presumably the protons are generated at the anode by oxidation of residual water and/or the solvent DMF. A major source of residual water could be the very hygroscopic tosylate as one of the reviewers suggested. The conditions of

A procedure for the preparation and isolation of nucleoside-5’-diphosphates

• Heidi J. Korhonen,
• Hannah L. Bolt and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2015, 11, 469–472, doi:10.3762/bjoc.11.52

• (triphenylphosphoranylidene)ammonium] pyrophosphate (PPN pyrophosphate) was used in the SN2 displacements of the tosylate ion from 5’-tosylnucleosides to afford nucleoside-5’-diphosphates. Selective precipitation permitted the direct isolation of nucleoside-5’-diphosphates from crude reaction mixtures. Keywords: NDP

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• conditions. Methyl acrylate (1a) was chosen as a model substrate as it is highly reactive in standard Matsuda–Heck reactions. Therefore, a solution of 4-nitrobenzenediazonium tosylate (2a) in water was allowed to react with 1.2 equiv of methyl acrylate (1a) in the presence of 1 mol % Pd(OAc)2 at rt, at 75 °C

• (t, 2H), 3.75 (t, 2H), 2.11 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 165.6, 142.6, 138.5, 132.7, 129.0, 121.4, 118.5, 112.3, 61.3, 41.8, 31.1; HRMS m/z: calcd. for C13H12NO2Cl, 249.0551; found, 249.0548. Arylation of methyl acrylate (1a) with arenediazonium tosylate 2a. Arylation of alkenes with ADT

• . Arylation of methyl acrylate (1a) with arenediazonium tosylate 2a. Study of reaction conditions. Arylation of alkenes with arenediazonium tosylates in water under microwave heating. Supporting Information Supporting Information File 354: Additional experimental data. Acknowledgements This research was

Photovoltaic-driven organic electrosynthesis and efforts toward more sustainable oxidation reactions

• Bichlien H. Nguyen,
• Robert J. Perkins,
• Jake A. Smith and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2015, 11, 280–287, doi:10.3762/bjoc.11.32

• needed. Another point of interest is related to the choice of the electrolyte for the reaction. The reactions highlighted in Scheme 2 provide an opportunity to address this issue. Typically, the choice of electrolyte is not crucial, and tetraethylammonium tosylate can be employed for the majority of

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• , finally, cholesteryl diphenylphosphate (5) was selected as the best cholesteryl donor [5]. Apart from these cholesterol derivatives, also simple alkyl or aryl ethers (6b–g) of 3α,5α-cyclocholestan-6β-ol (6a) (i-cholesterol) are readily available by solvolysis of cholesteryl p-tosylate in the corresponding

• cyclosteroid (i-steroid) rearrangement is a well-known steroid reaction [6]. The solvolysis of cholesteryl p-tosylate proceeds via the SN1 mechanism with the formation of a mesomerically stabilized carbocation. The addition of a nucleophile (alcohol, water, etc.) may occur either to C-3 or C-6, depending on

• –h was prepared including alkyl, aryl, and silyl ethers. Most of the compounds were prepared by solvolysis of cholesteryl p-tosylate in an appropriate alcohol (neat or mixed with dioxane) in the presence of potassium acetate as a buffer. TBDMS ether 6h was obtained by silylation of i-cholesterol 6a

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• -O-tosylate to β-CD-N3 following the procedures of Hocquelet et al. who also described the permethylated β-CD-N3 [39]. Furthermore, we headed for the regioselective 2,6-dimethylated product. Therefore β-CD-N3 was carefully methylated by dimethyl sulfate and a mixture of Ba(OH)2·8H2O and BaO as the